Phytophagy impacts the quality and quantity of plant carbon resources acquired by mutualistic arbuscular mycorrhizal fungi.

Arbuscular mycorrhizal (AM) fungi associate with the roots of many plant species, enhancing their hosts access to soil nutrients whilst obtaining their carbon supply directly as photosynthates. AM fungi often face competition for plant carbon from other organisms. The mechanisms by which plants prioritise carbon allocation to mutualistic AM fungi over parasitic symbionts remain poorly understood. Here, we show that host potato plants (Solanum tuberosum cv. Désirée) selectively allocate carbon resources to tissues interacting with AM fungi rather than those interacting with phytophagous parasites (the nematode Globodera pallida). We found that plants reduce the supply of hexoses but maintain the flow of plant-derived fatty acids to AM fungi when concurrently interacting with parasites. Transcriptomic analysis suggest that plants prioritise carbon transfer to AM fungi by maintaining expression of fatty acid biosynthesis and transportation pathways, whilst decreasing the expression of mycorrhizal-induced hexose transporters. We also report similar findings from a different plant host species (Medicago truncatula) and phytophagous pest (the aphid Myzus persicae). These findings suggest a general mechanism of plant-driven resource allocation in scenarios involving multiple symbionts.

Pre-targeting of polymeric nanomaterials to balance tumour accumulation and clearance.

Pre-targeting of bispecific antibodies is probed to enhance tumour retention while limiting clearance of administered multifunctional branched PEGylated nanomedicines. The temporal influence of pre-targeting on polymer interaction with tumour cells and tissue is explored using in vitro assays through to preclinical validation.

Dietary cholesterol increases ventricular volume and narrows cerebrovascular diameter in a rabbit model of Alzheimer's disease.

Using structural magnetic resonance imaging in a clinical scanner at 3.0T, we describe results showing that following 12weeks on a diet of 2% cholesterol, rabbits experience a significant increase in the volume of the third ventricle compared to rabbits on a diet of 0% cholesterol. Using time-of-flight magnetic resonance angiography, we find cholesterol-fed rabbits also experience a decrease in the diameter of a number of cerebral blood vessels including the basilar, posterior communicating, and internal carotid arteries. Taken together, these data confirm that, despite the inability of dietary cholesterol to cross the blood-brain barrier, it does significantly enlarge ventricular volume and decrease cerebrovascular diameter in the rabbit - effects that are also seen in patients with Alzheimer's disease.

Provider perceptions of pharmacy-initiated tuberculosis referral services in Cambodia, 2005-2010.

SETTING: Since 2005, private pharmacies linked to the National Tuberculosis Programme (NTP) and the Municipal Health Department in Phnom Penh have referred tuberculosis (TB) symptomatic patients to public sector TB clinics. OBJECTIVE: To investigate the attitudes and practices of pharmacy-initiated referral service providers in Phnom Penh from 2005 to 2010. METHODS: In a qualitative study, participants were purposively selected from the register of pharmacy owners providing referral services. Discussions were conducted in Khmer by trained facilitators. Participants discussed topics relating to their experiences and participation in the referral programme. RESULTS: In January 2011, 54 pharmacy owners participated in six focus group discussions held in Phnom Penh. Interpreted data showed consistency of message across all topics. The emergent themes-altruism, pragmatism and professionalism-underpinned owner commitment to programme goals. Issues associated with patient counselling, fear of infection and quality of care in public sector clinics were of concern to participants. Owners believed ongoing professional support, improved public sector patient care and media campaigns would strengthen their role. CONCLUSION: Pharmacy outlets provide further options for NTPs engaging with private sector providers. Recognising private provider needs and aspirations may be an essential component of public/private mix programmes to meet public health goals.

Knowledge, attitudes and practices of private sector providers of tuberculosis care: a scoping review.

SETTING: The past decade has seen a significant increase in private sector provision of tuberculosis (TB)care. While patients often seek and select treatment from private providers at significant out-of-pocket expense,treatment outcomes remain largely unknown. OBJECTIVE: To investigate the knowledge, attitudes and practices of private sector TB care providers in high burden countries. METHODS: Medline, PubMed, Embase, International Pharmaceutical Abstracts and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched using Medical Subject Headings terms,Emtree terms and key words. Searches were limited to the English language and published between 1998 and week 2 of November 2009. Studies were included if they reported the knowledge, attitudes or practice behaviours of private health care providers working in one of 22 high-TB-burden countries. Each included study was critically assessed using a structured data extraction tool. Data extracted included the study setting, objective, design, sample, response rate, outcomes and limitations. RESULTS: The 34 studies that met review inclusion criteriaen compassed diverse study methods and designs.All categories of TB care providers lacked comprehensive knowledge of national treatment guidelines. Procedures for referral, treatment monitoring, record keeping and case holding were not systematically implemented.However, there was a high degree of willingness to collaborate with national TB programmes. CONCLUSION: Research using standardised data collection methods may assist in identifying gaps in knowledge and practice among all providers of TB care. Further studies in developing and evaluating needs-based interventions should be undertaken; systematic reviews of such studies may then assist in strategic decision making in public-private mix DOTS expansion.

Prenatal exposure, maternal sensitization, and sensitization in utero to indoor allergens in an inner-city cohort.

Primary sensitization to antigens may occur prenatally. We hypothesized that high prenatal exposure to indoor antigens increases the risk for sensitization in newborns in New York City populations with increased risk for asthma. We also investigated whether maternal sensitization is required for in utero sensitization to occur. One hundred sixty-seven pregnant African American or Dominican women residing in northern Manhattan were recruited and antigen was measured from home dust. After delivery, newborn cord and maternal blood were assayed for IgE and mononuclear cell proliferation and cytokine production in response to antigen. Cockroach, mouse, but not dust mite antigens, were commonly elevated in the kitchens and pregnant mothers' beds. Increased mononuclear cell proliferation occurred in 54% of newborns in response to cockroach, 25% in response to dust mite Dermatophagoides pteronyssinus, 40% in response to dust mite D. farinae, and 34% in response to mouse protein extracts. Antigen-induced mononuclear cell proliferation occurred in cord blood even in the absence of antigen-induced mononuclear cell proliferation in the mother. Proliferation in response to antigens did not correlate with IgE levels, but proliferation in response to dust mite extracts correlated with interluekin-5 (IL-5) production in cord blood. These results suggest that (1) high prenatal exposures to cockroach and mouse antigens are prevalent; (2) in utero sensitization to multiple indoor antigens is common, occurs to a different degree than maternal sensitization, and may involve IL-5 upregulation.

Rotational coupling of the transmembrane and kinase domains of the Neu receptor tyrosine kinase.

Ligand binding to receptor tyrosine kinases (RTKs) regulates receptor dimerization and activation of the kinase domain. To examine the role of the transmembrane domain in regulation of RTK activation, we have exploited a simplified transmembrane motif, [VVVEVVV](n), previously shown to activate the Neu receptor. Here we demonstrate rotational linkage of the transmembrane domain with the kinase domain, as evidenced by a periodic activation of Neu as the dimerization motif is shifted across the transmembrane domain. These results indicate that activation requires a specific orientation of the kinase domains with respect to each other. Results obtained with platelet-derived growth factor receptor-beta suggest that this rotational linkage of the transmembrane domain to the kinase domain may be a general feature of RTKs. These observations suggest that activating mutations in RTK transmembrane and juxtamembrane domains will be limited to those residues that position the kinase domains in an allowed rotational conformation.

A study of commercial vehicle safety alliance's out-of-service criteria.

This paper summarizes a two-phase project that reviewed the Commercial Vehicle Safety Alliance's out-of-service criteria for vehicles. The first phase examined relevant background information and conducted a questionnaire survey of CVSA inspectors and industry representatives. The second phase of the project involved extensive collection and evaluation of accident data. The results of both phases show a high level of support, in terms of contribution to vehicle accidents, for four of the vehicle criteria (regarding brakes, load securement, tires, and wheels and rims). There was some support for coupling devices, fuel systems, lighting devices, steering and suspension. The support for the remaining vehicle criteria (exhaust systems, frames, van and open top trailer bodies, and windshield wipers) was little to none. Further research continuing the study of accident data is recommended to confirm these findings. However, the data must be collected in a consistent and detailed manner if accurate information on the relationship of accidents and vehicle criteria is to be established.

Structure-activity studies of dicationically substituted bis-benzimidazoles against Giardia lamblia: correlation of antigiardial activity with DNA binding affinity and giardial topoisomerase II inhibition.

Nine dicationically substituted bis-benzimidazoles were examined for their in vitro activities against Giardia lamblia WB (ATCC 30957). The potential mechanisms of action of these compounds were evaluated by investigating the relationship among in vitro antigiardial activity and the affinity of the molecules for DNA and their ability to inhibit the activity of giardial topoisomerase II. Each compound demonstrated antigiardial activity, as measured by assessing the incorporation of [methyl-3H]thymidine by giardial trophozoites exposed to the test agents. Three compounds exhibited excellent in vitro antigiardial activities, with 50% inhibitory concentrations which compared very favorably with those of two currently used drugs, quinacrine HCl and metronidazole. Putative mechanisms of action for these compounds were suggested by the strong correlation observed among in vitro antigiardial activity and the affinity of the molecules for natural and synthetic DNA and their ability to inhibit the relaxation activity of giardial topoisomerase II. A strong correlation between the DNA binding affinity of these compounds and their inhibition of giardial topoisomerase II activity was also observed.

Assessing the hemodynamic significance of coronary artery stenoses: analysis of translesional pressure-flow velocity relations in patients.

OBJECTIVES: The purpose of this study was to examine the relation among the angiographic severity of coronary artery lesions, coronary flow velocity and translesional pressure gradients. BACKGROUND: Determination of the clinical and hemodynamic significance of coronary artery stenoses is often difficult and inexact. Angiography has been shown to be an imperfect tool for determining the physiologic significance of eccentric or irregular coronary lumen narrowing. METHODS: Using a 0.018-in. (0.046 cm) intracoronary Doppler-tipped angioplasty guide wire, spectral flow velocity data both proximal and distal to coronary stenoses were compared with translesional pressure gradient measurements and angiographic data obtained during cardiac catheterization in 101 patients. There were 17 patients with normal angiographic findings and 84 with coronary artery disease, with lesions ranging from 28% to 99% diameter narrowing. Patients with coronary disease were assigned to two groups on the basis of translesional gradients at rest. Group A (n = 56) had gradients < 20 mm Hg, and Group B (n = 28) had gradients > or = 20 mm Hg. RESULTS: Proximal average peak velocity, diastolic velocity integral and total velocity integral were slightly but statistically lower in Group A; however, the distal average peak velocity and diastolic and total velocity integrals were all markedly (all p < 0.01) decreased in patients with gradients > or = 20 mm Hg (Group B). In addition, the ratio of proximal to distal total flow velocity integral was higher in Group B (2.4 +/- 1.0) than in group A (1.1 +/- 0.3, p < 0.001). There was a strong correlation between translesional pressure gradients and the ratios of the proximal to distal total flow velocity integrals (r = 0.8, p < 0.001), with a weaker relation between quantitative angiography and pressure gradients (r = 0.6, p < 0.001). In angiographically intermediate stenoses (range 50% to 70%), angiography was a poor predictor of translesional gradients (r = 0.2, p = NS), whereas the flow velocity ratios continued to have a strong correlation (r = 0.8, p < 0.001). Only two patients with a proximal/distal total flow velocity ratio < 1.7 had a translesional gradient > 30 mm Hg. Both patients had a very proximal lesion in a nonbranching right coronary artery. CONCLUSIONS: These data demonstrate that in branching human coronary arteries, a close relation exists between translesional hemodynamics and distal coronary flow velocity. Translesional coronary flow velocity is a new and easily applicable method for determining the hemodynamic significance of coronary artery stenoses that is superior to angiography and can be applied at the time of diagnostic catheterization. These data will provide a rational approach to making decisions on the use of coronary interventional techniques when angiographic findings are questionable.

Knockdown resistance (kdr) to DDT and pyrethroid insecticides maps to a sodium channel gene locus in the housefly (Musca domestica).

The voltage-sensitive sodium channel is generally regarded as the primary target site of dichloro-diphenyl-trichloro-ethane (DDT) and pyrethroid insecticides, and has been implicated in the widely reported mechanism of nerve insensitivity to these compounds. This phenomenon is expressed as knockdown resistance (kdr) and has been best characterised in the housefly where several putative alleles, including the more potent super-kdr factor, have been identified. We report the isolation of cDNA clones containing part of a housefly sodium channel gene, designated Msc, which show close homology to the para sodium channel of Drosophila (99% amino acid identity within the region of overlap). Using Southern blots of insect DNA, restriction fragment length polymorphisms (RFLPs) at the Msc locus were identified in susceptible, kdr and super-kdr housefly strains. These RFLPs showed tight linkage to resistance in controlled crosses involving these strains, thus providing clear genetic evidence that kdr, and hence pyrethroid mode of action, is closely associated with the voltage-sensitive sodium channel.

Superior accuracy of anatomic positioning with echocardiographic- over fluoroscopic-guided endomyocardial biopsy.

To assess the superior anatomic positioning of echocardiographic-guided endomyocardial biopsy compared to traditional fluoroscopic-guided technique, these two modalities were compared in a blinded fashion during femoral sheath endomyocardial biopsy in 21 patients, 19 being evaluated after orthotopic cardiac transplantation. The simultaneous fluoroscopic and echocardiographic imaging indicated that traditional fluoroscopic positioning of the bioptome against the septum is inaccurate in over half of patients undergoing biopsy. This finding should be considered in cardiomyopathy patients or those at high risk for biopsy-related complications.

Structure-activity relationships of pentamidine analogs against Giardia lamblia and correlation of antigiardial activity with DNA-binding affinity.

1,5-Di(4-amidinophenoxy)pentane (pentamidine) and 38 analogs of pentamidine were screened for in vitro activity against the enteric protozoan Giardia lamblia WB (ATCC 30957). All compounds were active against G. lamblia as measured by a [methyl-3H]thymidine incorporation assay. Antigiardial activity varied widely, with 50% inhibitory concentrations (IC50s) ranging from 0.51 +/- 0.13 microM (mean +/- standard deviation) for the most active compound to over 100.0 microM for the least active compounds. The IC50 of the most potent antigiardial agent, 1,3-di(4-amidino-2-methoxyphenoxy)propane compared favorably with the IC50s of the compounds currently used to treat giardiasis, i.e., furazolidone (1.0 +/- 0.03 microM), metronidazole (2.1 +/- 0.80 microM), quinacrine HCl (0.03 +/- 0.02 microM), and tinidazole (0.78 +/- 0.48 microM). A mode of antigiardial activity for these compounds was suggested by the correlation observed between antigiardial activity and the binding of the compounds to calf thymus DNA and poly(dA).poly(dT).

Female homicides in United States workplaces, 1980-1985.

BACKGROUND: Women, while noted for low occupational injury mortality rates, are more likely to die as victims of assault than from any other manner of injury at work. METHODS: From the National Traumatic Occupational Fatality surveillance data, 950 women were identified who were fatally assaulted at work. Homicide rates were calculated for the demographic and employment characteristics of these women. Risk ratios among types of lethal injuries were examined. RESULTS: During 1980-1985, the crude six-year workplace homicide rate was 4.0 deaths per million working women: one twentieth the homicide rate of the US female population. Decedents ranged from 16 years (the lowest age included in the data base) to 93 years of age. Working women older than 65 years had the highest age-specific homicide rate, 11.3 per million. Women younger than 20 had the lowest, 2.5 per million per year. Homicide rates for women of races other than White were nearly twice as high as those of Whites. The leading causes of death were gunshot wounds (64 percent), stabbings (19 percent), asphyxiations (7 percent), and blunt force trauma (6 percent). Nearly 43 percent of the deceased women had been employed in retail trade: 8.7 per million employed women annually. CONCLUSIONS: During 1980-1985, only 6 percent of the nation's victims of work-related injury deaths were female: 41 percent of those women were murdered. Homicide is currently the leading manner of traumatic workplace death among women in the United States.

Metabolic N-hydroxylation of pentamidine in vitro.

By using high-performance liquid chromatography, the in vitro conversion of pentamidine to the corresponding amidoximes (N-hydroxypentamidine and N,N'-dihydroxypentamidine) was studied in supernatants of rat liver homogenate centrifuged at 9,000 x g. The presence of the two amidoxime peaks in chromatograms was confirmed by liquid secondary ion mass spectrometry and by unequivocal synthesis of the suspected metabolites. The metabolic reactions were found to be catalyzed by the cytochrome P-450 system (mixed-function oxidases). The formation of the monohydroxylated product was found to have a Km of 0.48 mM and a Vmax of 29.50 pmol/min per mg of protein, while the dihydroxylated metabolite had a Km of 0.73 mM and a Vmax of 4.10 pmol/min per mg of protein. N,N'-Dihydroxypentamidine was found to have highly reduced antiprotozoal activity in vitro relative to that of pentamidine, and neither of the hydroxylated metabolites nor pentamidine was found to be significantly mutagenic by the Ames test. Contrary to previous reports, pentamidine is readily metabolized to at least two hydroxylated products, and this conversion may be relevant to the clinical use of the compound and to future drug design.

Structure-activity relationships of analogs of pentamidine against Plasmodium falciparum and Leishmania mexicana amazonensis.

The antiprotozoal compound 1,5-di(4-amidinophenoxy)pentane (pentamidine) and 36 of its analogs were screened for in vitro activity against Leishmania mexicana amazonensis clone 669 C4S (MHOM/BR/73/M2269) and Plasmodium falciparum clones W2 (Indochina III/CDC) and D6 (Sierra Leone I/CDC). Pentamidine and each of the analogs tested exhibited activity in vitro against L. m. amazonensis and P. falciparum. The pentamidine analogs were more effective against the P. falciparum clones than against L. m. amazonensis. P. falciparum was extremely susceptible to these compounds, with 50% inhibitory concentrations as low as 0.03 microM. While none of the analogs exhibited marked improvement in antileishmanial activity compared with pentamidine, 12 of the pentamidine analogs showed activity approximately equal to or greater than that of the parent compound. From the promising activity exhibited by the pentamidine analogs in this in vitro study and their potential for reduced toxicity relative to the parent drug, pentamidine-related compounds hold promise as new agents for the treatment of protozoal infections.

Fatal occupational injuries in the United States, 1980 through 1985.

The National Traumatic Occupational Fatality surveillance project was designed to gather demographic, employment, and injury information from death certificates for all deaths due to injuries at work in the United States. Approximately 7000 workers have died each year during the 6-year period from 1980 through 1985: 94% were men, and 6% were women. Unintentional injuries caused the deaths of 83% of the men and 50% of the women. Eleven percent of the men and 39% of the women died from homicide. While the greatest number of deaths occurred in the group aged 20 through 34 years, fatality rates were highest among those aged 70 years and older. Expressed as deaths per 100,000 workers, annual fatality rates for black workers (7.7) were slightly higher than for white workers (6.5). The four industrial groups with the highest fatality rates were mining (31.9); transportation, communication, and public utilities (25.4); construction (24.0); and agriculture, forestry, and fishing (20.7). From 1980 through 1985 the annual traumatic occupational fatality rate fell 23%.